This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. There is clearly an association between HIV infection and alcohol use. However, determining whether alcohol intake results in physiologic or immunologic conditions that increase the risk or susceptibility to infection rather than simply resulting in persons engaging in riskier behavior simply cannot be easily deciphered in humans. We are continuing to examine the interaction SIV and alcohol use in the well-controlled macaque model, which can distinguish these factors. This year we began a new series of studies based on intestinal permeability and cell proliferation to determine whether alcohol accelerates the pathogenesis of infection and disease progression with SIV. We are measuring the effects of alcohol use on release of intestinal and/or bacterial byproducts into the systemic circulation, whether this increases systemic or local inflammation, and whether these factors increase the rates of T cell destruction or turnover in intestinal and peripheral lymphoid tissues. We have assigned and started 8 male macaques and are currently testing their mucosal and systemic immune responses to SIV infection while on alcohol. In another series we are looking at the same effects on the female reproductive tract to see if alcohol increases inflammation in the vagina and/or whether this could increase the rate of vaginal HIV transmission. Four female animals have been assigned to date for these studies.